Effects of novobiocin on pituitary-thyroid axis in the rat and its mechanism

Abstract

Graded doses (20 to 60 mg.) of novobiocin were injected subcutaneously daily for varying periods of time, and effects of those injections on thyroid weight, thyroidal radioiodine uptake, organic binding of iodine, thyroidal radioiodine release, blood PBI and thyroxine-plasma protein interaction were studied in the rat. Administration of 20 or 40 mg. novobiocin for 7 days produced a low blood PBI without affecting thyroid weight, thyroidal radioiodine uptake and organic binding of iodine. However, thyroidal radioiodine uptake was suppressed at the beginning of the drug administration but it returned to normal by 2 days. In contrast, large doses of novobiocin for 7 days suppressed thyroidal radioiodine uptake and blood PBI. Since the novobiocin-suppressed thyroidal radioiodine release could be accelerated by the administration of exogenous TSH, and since novobiocin did not suppress adrenocortical and gonadal activity, those transitory and continuous inhibitions of thyroid activity might be produced by a decrease of TSH secretion. Muscle uptake of labeled thyroxine was high in the presence of plasma obtained from novobiocin-treated animals or in the presence of plasma with added novobiocin in vitro. Novobiocin was without effect on muscle uptake of thyroxine in the absence of plasma. Electrophoretic study indicated that novobiocin displaced thyroxine from albumin in vitro. It is suggested that novobiocin produced a low blood PBI by displacing thyroxine from albumin. The transitory inhibition of thyroid activity produced by small doses of novobiocin suggests the pattern reaching a new equilibrium in which thyroxine-plasma protein interaction is impaired. A new equilibrium may not be established by 7 days when large doses of novobiocin are administered in the rat.